Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration
Iron homeostasis plays an important role in maintaining cellular homeostasis; however, excessive iron can promote the production of reactive oxygen species (ROS). Ferroptosis is iron-dependent programmed cell death that is characterized by excessive iron accumulation, elevated lipid peroxides, and t...
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2025-04-01
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| author | Na Zhao Siyu Li Hao Wu Dong Wei Ning Pu Kexin Wang Yashuang Liu Ye Tao Zongming Song |
| author_facet | Na Zhao Siyu Li Hao Wu Dong Wei Ning Pu Kexin Wang Yashuang Liu Ye Tao Zongming Song |
| author_sort | Na Zhao |
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| description | Iron homeostasis plays an important role in maintaining cellular homeostasis; however, excessive iron can promote the production of reactive oxygen species (ROS). Ferroptosis is iron-dependent programmed cell death that is characterized by excessive iron accumulation, elevated lipid peroxides, and the overproduction of ROS. The maintenance of iron homeostasis is contingent upon the activity of the transferrin receptor (TfR), ferritin (Ft), and ferroportin (FPn). In the retina, iron accumulation and lipid peroxidation can contribute to the development of age-related macular degeneration (AMD). This phenomenon can be explained by the occurrence of the Fenton reaction, in which the interaction between divalent iron and hydrogen peroxide leads to the generation of highly reactive hydroxyl radicals. The hydroxyl radicals exhibit a propensity to attack proteins, lipids, nucleic acids, and carbohydrates, thereby instigating oxidative damage and promoting lipid peroxidation. Ultimately, these processes culminate in cell death and retinal degeneration. In this context, a comprehensive understanding of the exact mechanisms underlying ferroptosis may hold significant importance for developing therapeutic interventions. This review summarizes recent findings on iron metabolism, cellular ferroptosis, and lipid metabolism in the aging retina. We also introduce developments in the therapeutic strategies using iron chelating agents. Further refinements of these knowledges would deepen our comprehension of the pathophysiology of AMD and advance the clinical management of degenerative retinopathy. A comprehensive search strategy was employed to identify relevant studies on the role of ferroptosis in AMD. We performed systematic searches of the PubMed and Web of Science electronic databases from inception to the current date. The keywords used in the search included “ferroptosis”, “AMD”, “age-related macular degeneration”, “iron metabolism”, “oxidative stress”, and “ferroptosis pathways”. Peer-reviewed articles, including original research, reviews, meta-analyses, and clinical studies, were included in this paper, with a focus on the molecular mechanisms of ferroptosis in AMDs. Studies not directly related to ferroptosis, iron metabolism, or oxidative stress in the context of AMD were excluded. Furthermore, articles that lacked sufficient data or were not peer-reviewed (e.g., conference abstracts, editorials, or opinion pieces) were not considered. |
| format | Article |
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| publishDate | 2025-04-01 |
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| spelling | doaj-art-a584c1d21e664a27a9bfb4c15cd2b4822025-08-20T02:17:19ZengMDPI AGBiomedicines2227-90592025-04-0113498610.3390/biomedicines13040986Ferroptosis: An Energetic Villain of Age-Related Macular DegenerationNa Zhao0Siyu Li1Hao Wu2Dong Wei3Ning Pu4Kexin Wang5Yashuang Liu6Ye Tao7Zongming Song8Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan University School of Medicine, Henan Provincial People’s Hospital, Zhengzhou 450003, ChinaCollege of Medicine, Zhengzhou University, Zhengzhou 450001, ChinaCollege of Medicine, Zhengzhou University, Zhengzhou 450001, ChinaCollege of Medicine, Zhengzhou University, Zhengzhou 450001, ChinaCollege of Medicine, Zhengzhou University, Zhengzhou 450001, ChinaHenan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan University School of Medicine, Henan Provincial People’s Hospital, Zhengzhou 450003, ChinaHenan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan University School of Medicine, Henan Provincial People’s Hospital, Zhengzhou 450003, ChinaHenan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan University School of Medicine, Henan Provincial People’s Hospital, Zhengzhou 450003, ChinaHenan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan University School of Medicine, Henan Provincial People’s Hospital, Zhengzhou 450003, ChinaIron homeostasis plays an important role in maintaining cellular homeostasis; however, excessive iron can promote the production of reactive oxygen species (ROS). Ferroptosis is iron-dependent programmed cell death that is characterized by excessive iron accumulation, elevated lipid peroxides, and the overproduction of ROS. The maintenance of iron homeostasis is contingent upon the activity of the transferrin receptor (TfR), ferritin (Ft), and ferroportin (FPn). In the retina, iron accumulation and lipid peroxidation can contribute to the development of age-related macular degeneration (AMD). This phenomenon can be explained by the occurrence of the Fenton reaction, in which the interaction between divalent iron and hydrogen peroxide leads to the generation of highly reactive hydroxyl radicals. The hydroxyl radicals exhibit a propensity to attack proteins, lipids, nucleic acids, and carbohydrates, thereby instigating oxidative damage and promoting lipid peroxidation. Ultimately, these processes culminate in cell death and retinal degeneration. In this context, a comprehensive understanding of the exact mechanisms underlying ferroptosis may hold significant importance for developing therapeutic interventions. This review summarizes recent findings on iron metabolism, cellular ferroptosis, and lipid metabolism in the aging retina. We also introduce developments in the therapeutic strategies using iron chelating agents. Further refinements of these knowledges would deepen our comprehension of the pathophysiology of AMD and advance the clinical management of degenerative retinopathy. A comprehensive search strategy was employed to identify relevant studies on the role of ferroptosis in AMD. We performed systematic searches of the PubMed and Web of Science electronic databases from inception to the current date. The keywords used in the search included “ferroptosis”, “AMD”, “age-related macular degeneration”, “iron metabolism”, “oxidative stress”, and “ferroptosis pathways”. Peer-reviewed articles, including original research, reviews, meta-analyses, and clinical studies, were included in this paper, with a focus on the molecular mechanisms of ferroptosis in AMDs. Studies not directly related to ferroptosis, iron metabolism, or oxidative stress in the context of AMD were excluded. Furthermore, articles that lacked sufficient data or were not peer-reviewed (e.g., conference abstracts, editorials, or opinion pieces) were not considered.https://www.mdpi.com/2227-9059/13/4/986age-related macular degenerationironlipid peroxidationferroptosis |
| spellingShingle | Na Zhao Siyu Li Hao Wu Dong Wei Ning Pu Kexin Wang Yashuang Liu Ye Tao Zongming Song Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration Biomedicines age-related macular degeneration iron lipid peroxidation ferroptosis |
| title | Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration |
| title_full | Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration |
| title_fullStr | Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration |
| title_full_unstemmed | Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration |
| title_short | Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration |
| title_sort | ferroptosis an energetic villain of age related macular degeneration |
| topic | age-related macular degeneration iron lipid peroxidation ferroptosis |
| url | https://www.mdpi.com/2227-9059/13/4/986 |
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